There is a need for new technologies to enable the analysis of the proteome. We propose to develop a novel technology for analyzing protease activity. Proteases are involved in the regulation of essential cellular processes and misregulation of proteolytic activity is involved in many diseases such as neurodegeneration, cardiovascular diseases, arthritis, Alzheimer's disease, cancer, and infectious diseases. PUBLIC HEALTH RELEVANCE: The protease activity profiling technology we are developing is useful for identifying new protease drug targets for drug development. It would help to elucidate the functional roles of specific proteases and may result in advances in the diagnosis and treatment of disease.